摘要
目的:探讨Survivin及其异变体(Survivin-2B和Survivin-△Ex3)、P53和MDM2在柔红霉素(DNR)诱导白血病Jurkat细胞凋亡中的变化。方法:DNR设0.1mg/L、1mg/L、10mg/L 3个浓度,作用Jurkat细胞12h、24h后,用RT-PCR方法检测Survivin、Survivin-2B、Survivin-△Ex3、P53及MDM2基因的mRNA表达变化,用Western-blot方法检测同样条件下Survivin、P53及MDM2蛋白表达的变化。结果:在mRNA水平,DNR抑制Survivin、Survivin-△Ex3表达,促进Survivin-2B、P53表达,具有时间与浓度依赖性(P<0.05);DNR抑制MDM2表达表现出时间依赖性和不完全浓度依赖性(P<0.05)。在蛋白水平,DNR以时间和浓度依赖方式抑制Survivin、MDM2表达,促进P53表达(P<0.05)。结论:DNR通过下调Survivin、Survivin-△Ex3、MDM2表达,上调Survivin-2B、P53表达,从而诱导Jurkat细胞凋亡,且呈时间和浓度依赖性。通过干扰Survivin、Survivin-△Ex3及MDM2的表达,有望提高白血病细胞对DNR的敏感性,从而提高临床缓解率及预后。
Objective：To investigate the change of Survivin and its splice variants（Survivin-2B and Survivin-△Ex3）,P53,MDM2 in the apoptosis of Jurkat cell induced by Daunorubicin（DNR）. Method：Jurkat cell was treated by DNR with different concentrations（0.1 mg/L,1 mg/L,10 mg/L） for 12 h and 24 h.Survivin,Survivin-2B,Survivin-△Ex3,P53 and MDM2 mRNA were measured by RT-PCR.The expression of Survivin,P53,MDM2 proteins were detected by Western-blot. Result：The mRNA expressions of Survivin and Survivin-△Ex3 were inhibited by DNR in time-and dose-dependent manners,but the mRNA expressions of Survivin-2B and P53 were improved（P0.05）.The mRNA expression of MDM2 was inhibited by DNR in time-dependent manner and not all dose-dependent manner（P0.05）.Survivin and MDM2 proteins decreased by DNR in time-and dose-dependent manners,but P53 protein increased（P0.05）. Conclusion：DNR induces the apoptosis of Jurkat cell not only through inhibiting the expressions of Survivin,Survivin-△Ex3 and MDM2 but also improving the expressions of Survivin-2B and P53 in time-and dose-dependent manners.Leukemia cells may become susceptive to DNR via disturbing the expressions of Survivin,Survivin-△Ex3 and MDM2,thereby improving clinical remission rate and prognosis.
出处
《临床血液学杂志》
CAS
2013年第4期482-484,487,共4页
Journal of Clinical Hematology
